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Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding

Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infec...

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Autores principales: Wittwer, Kevin, Anderson, Danielle E., Pfeffermann, Kristin, Cox, Robert M., Wolf, Josef D., Santibanez, Sabine, Mankertz, Annette, Plesker, Roland, Sticher, Zachary M., Kolkykhalov, Alexander A., Natchus, Michael G., Pfaller, Christian K., Plemper, Richard K., von Messling, Veronika
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413292/
https://www.ncbi.nlm.nih.gov/pubmed/34475387
http://dx.doi.org/10.1038/s41467-021-25497-4
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author Wittwer, Kevin
Anderson, Danielle E.
Pfeffermann, Kristin
Cox, Robert M.
Wolf, Josef D.
Santibanez, Sabine
Mankertz, Annette
Plesker, Roland
Sticher, Zachary M.
Kolkykhalov, Alexander A.
Natchus, Michael G.
Pfaller, Christian K.
Plemper, Richard K.
von Messling, Veronika
author_facet Wittwer, Kevin
Anderson, Danielle E.
Pfeffermann, Kristin
Cox, Robert M.
Wolf, Josef D.
Santibanez, Sabine
Mankertz, Annette
Plesker, Roland
Sticher, Zachary M.
Kolkykhalov, Alexander A.
Natchus, Michael G.
Pfaller, Christian K.
Plemper, Richard K.
von Messling, Veronika
author_sort Wittwer, Kevin
collection PubMed
description Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication.
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spelling pubmed-84132922021-09-22 Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding Wittwer, Kevin Anderson, Danielle E. Pfeffermann, Kristin Cox, Robert M. Wolf, Josef D. Santibanez, Sabine Mankertz, Annette Plesker, Roland Sticher, Zachary M. Kolkykhalov, Alexander A. Natchus, Michael G. Pfaller, Christian K. Plemper, Richard K. von Messling, Veronika Nat Commun Article Measles virus (MeV) is a highly contagious pathogen that enters the human host via the respiratory route. Besides acute pathologies including fever, cough and the characteristic measles rash, the infection of lymphocytes leads to substantial immunosuppression that can exacerbate the outcome of infections with additional pathogens. Despite the availability of effective vaccine prophylaxis, measles outbreaks continue to occur worldwide. We demonstrate that prophylactic and post-exposure therapeutic treatment with an orally bioavailable small-molecule polymerase inhibitor, ERDRP-0519, prevents measles disease in squirrel monkeys (Saimiri sciureus). Treatment initiation at the onset of clinical signs reduced virus shedding, which may support outbreak control. Results show that this clinical candidate has the potential to alleviate clinical measles and augment measles virus eradication. Nature Publishing Group UK 2021-09-02 /pmc/articles/PMC8413292/ /pubmed/34475387 http://dx.doi.org/10.1038/s41467-021-25497-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Wittwer, Kevin
Anderson, Danielle E.
Pfeffermann, Kristin
Cox, Robert M.
Wolf, Josef D.
Santibanez, Sabine
Mankertz, Annette
Plesker, Roland
Sticher, Zachary M.
Kolkykhalov, Alexander A.
Natchus, Michael G.
Pfaller, Christian K.
Plemper, Richard K.
von Messling, Veronika
Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
title Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
title_full Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
title_fullStr Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
title_full_unstemmed Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
title_short Small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
title_sort small-molecule polymerase inhibitor protects non-human primates from measles and reduces shedding
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413292/
https://www.ncbi.nlm.nih.gov/pubmed/34475387
http://dx.doi.org/10.1038/s41467-021-25497-4
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